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Antibacterial Activity and Membrane-Targeting Mechanism of Aloe-Emodin Against Staphylococcus epidermidis.

ABSTRACT: The emergence of multidrug-resistant Staphylococcus epidermidis (S. epidermidis) dwarfs the current antibiotic development and calls for the discovery of new antibacterial agents. Aloe-emodin is a plant-derived compound that holds promise to battle against these strains. This work reports the antimicrobial activity of aloe-emodin against S. epidermidis and other Gram-positive pathogenic species, manifesting minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBCs) around 4-32 and 32-128 μg/mL, respectively. For Gram-negative bacteria tested, the MICs and MBCs of aloe-emodin were 128-256 and above 1024 μg/mL, respectively. Aloe-emodin at the MBC for 4 h eradicated 96.9% of S. epidermidis cells. Aloe-emodin treatment led to deformities in the morphology of S. epidermidis cells and the destroy of the selective permeability of the cell membranes. Analysis of the transcriptional profiles of aloe-emodin-treated cells revealed changes of genes involved in sulfur metabolism, L-lysine and peptidoglycan biosynthesis, and biofilm formation. Aloe-emodin therefore can safely control Gram-positive bacterial infections and proves to target the bacterial outer membrane.

SUBMITTER: Li T

PROVIDER: S-EPMC8415635 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multidrug resistance among various bacterial strains is leading to worldwide resistance to a wide range of antibiotics. Combination therapy involving current antibiotics and other biological or chemical molecules represents an attractive novel strategy. In this study, we investigated the synergistic antibacterial activity of a series of Trp-containing antimicrobial peptides (AMPs) with four classes of traditional chemical antibiotics that are inactive against multidrug-resistant Staphylococcus epidermidis (MRSE) in vitro and in vivo. Among the antibiotics that we studied, penicillin, ampicillin and erythromycin showed a distinct synergistic effect in combination with all of the Trp-containing AMPs, represented by a fractional inhibitory concentration index (FICI) of <0.5. The antibacterial activities were noticeably improved, with 32-to 64-fold reductions in the MIC values for ampicillin and 16- to 32-fold reductions in the MIC values for erythromycin and penicillin. Tetracycline showed synergistic activity with only I1WL5W but additive activity with L11W, L12W, and I4WL5W. Ceftazidime exhibited additive activity with the Trp-containing peptides. In addition, the antibiotics in combination with the peptide significantly inhibited biofilm formation by MRSE 1208. A mechanistic study demonstrated that the Trp-containing peptides, especially I1WL5W and I4WL5W, which contain two tryptophan residues, disrupted bacterial inner and outer membranes, which promoted antibiotic delivery into the cytoplasm and access to cytoplasmic targets; however, L11W and L12W may have increased intracellular antibiotic concentrations by decreasing blaZ, tet(m) and msrA expression. Importantly, strong synergistic activity against the MRSE 1208 strain was observed for the combination of I1WL5W and penicillin in a mouse infection model. Thus, the combination of AMPs and traditional antibiotics could be a promising option for the prevention of acute and chronic infections caused by MRSE.

Project description:Aloe arborescens is a relevant species largely used in traditional medicine of several countries. In particular, the decoction of leaves is prepared for various medicinal purposes including antidiabetic care. The aim of this research was the study of the antiglycation activity of two A. arborescens leaf extracts and isolated compounds: aloin and aloe-emodin. These phytoconstituents were quantitatively assessed in methanolic and hydroalcoholic extracts using high performance liquid chromatography (HPLC) analysis. In addition, the total phenolic and flavonoid contents were detected. In order to study their potential use in diabetic conditions, the antiglycation and antiradical properties of the two extracts and aloin and aloe-emodin were investigated by means of bovine serum albumin (BSA) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays; further, their cytotoxicity in HT-29 human colon adenocarcinoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, the ability of aloin and aloe-emodin to permeate the cellular membranes of HT-29 cells was determined in order to estimate their potential in vivo absorption. This assessment indicated that aloe-emodin can substantially pass through cell membranes (~20%), whereas aloin did not permeate into HT-29 cells. Overall, the data show that both the methanolic and the hydroalcoholic A. arborescens extracts determine significant inhibition of glycation and free-radical persistence, without any cytotoxic activity. The data also show that the antiglycation and the antiradical activities of aloin and aloe-emodin are lower than those of the two extracts. In relation to the permeability study, only aloe-emodin is able to cross HT-29 cellular membranes, showing the attitude to pass through the intestinal layer. Overall, the present data surely support the traditional use of A. arborescens leaf extracts against hyperglycemic conditions, while aloin and aloe-emodin as potential drugs need further study.

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Antibacterial Activity and Membrane-Targeting Mechanism of Aloe-Emodin Against Staphylococcus epidermidis.

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